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- W4317584389 abstract "Abstract Repurposing drugs capable of extending lifespan and health span has a huge untapped potential in translational geroscience. Here, we searched for known compounds that elicit a similar gene expression signature to caloric restriction and identified rilmenidine, an I1‐imidazoline receptor agonist and prescription medication for the treatment of hypertension. We then show that treating Caenorhabditis elegans with rilmenidine at young and older ages increases lifespan. We also demonstrate that the stress‐resilience, health span, and lifespan benefits of rilmenidine treatment in C. elegans are mediated by the I1‐imidazoline receptor nish‐1 , implicating this receptor as a potential longevity target. Consistent with the shared caloric‐restriction‐mimicking gene signature, supplementing rilmenidine to calorically restricted C. elegans , genetic reduction of TORC1 function, or rapamycin treatment did not further increase lifespan. The rilmenidine‐induced longevity required the transcription factors FOXO/DAF‐16 and NRF1,2,3/SKN‐1. Furthermore, we find that autophagy, but not AMPK signaling, was needed for rilmenidine‐induced longevity. Moreover, transcriptional changes similar to caloric restriction were observed in liver and kidney tissues in mice treated with rilmenidine. Together, these results reveal a geroprotective and potential caloric restriction mimetic effect by rilmenidine that warrant fresh lines of inquiry into this compound." @default.
- W4317584389 created "2023-01-21" @default.
- W4317584389 creator A5009458380 @default.
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- W4317584389 creator A5080253914 @default.
- W4317584389 date "2023-01-20" @default.
- W4317584389 modified "2023-10-15" @default.
- W4317584389 title "Rilmenidine extends lifespan and healthspan in <i>Caenorhabditis elegans</i> via a nischarin <scp>I1</scp> ‐imidazoline receptor" @default.
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- W4317584389 doi "https://doi.org/10.1111/acel.13774" @default.
- W4317584389 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36670049" @default.
- W4317584389 hasPublicationYear "2023" @default.
- W4317584389 type Work @default.